Summary

• Janssen does not recommend any practices, procedures, or usage that deviate from the product labeling or are not approved by regulatory agencies.
• MajesTEC-4 (EMN30; MMY3003) is an open-label, randomized, multicenter, phase 3 study assessing the efficacy and safety of TECVAYLI in combination with lenalidomide (Tec-Len) and TECVAYLI alone vs lenalidomide alone as maintenance therapy after autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (NDMM).^1-3 
  • Zamagni et al (2024)³ presented the preliminary efficacy and safety results from the safety run-in (SRI) of Cohort 1 (Tec-Len; TECVAYLI weekly [QW] to every 4 weeks [Q4W]) at a median follow-up of 21.1 months (range, 14.8-23.8), Cohort 2 (Tec-Len; TECVAYLI Q4W) at a median follow-up of 9.2 months (range, 1.2-12.2), and Cohort 3 (TECVAYLI [Q4W]) at a median follow-up of 9.2 months (range, 3.7- 11.5).

CLINICAL DATA - MAJESTEC-4 STUDY

MajesTEC-4 (EMN30; MMY3003; clinicaltrials.gov identifier NCT05243797) is an open-label, randomized, multicenter, phase 3 study evaluating the efficacy and safety of Tec-Len and TECVAYLI alone vs lenalidomide alone as maintenance therapy in patients with NDMM.^1,3

Study Design/Methods

• The study design is presented in the Figure: MajesTEC-4/EMN30 Study Design.
• An SRI period consisting of 3 cohorts was used to establish safety prior to enrolling the randomized phase of the study.³
• Maintenance regimen (2-year fixed duration): patients who achieved complete response (CR) on Tec-Len after 1-year discontinued TECVAYLI and continued lenalidomide for an additional year.

Zamagni et al (2024)³ presented the preliminary efficacy and safety results from the SRI of Cohort 1 (Tec-Len; TECVAYLI QW to Q4W) at a median follow-up of 21.1 months (range, 14.8-23.8), Cohort 2 (Tec-Len; TECVAYLI Q4W) at a median follow-up of 9.2 months (range, 1.2-12.2), and Cohort 3 (TECVAYLI [Q4W]) at a median follow-up of 9.2 months (range, 3.7- 11.5).

Results

Treatment Disposition

• Median time from ASCT to enrollment for all patients was 4.7 months (range, 1.8-7.4).
• Baseline characteristics and demographics are presented in Table: MajesTEC-4/EMN30 Study (SRI Cohorts): Demographics and Disease Characteristics .
• As of September 9, 2024, 81 out of 94 patients (86.2%) remained on treatment. See Table: MajesTEC-4/EMN30 Study (SRI Cohorts): Treatment Disposition and Exposure for additional details.

Efficacy

• Response rates were evaluated for SRI Cohorts 1, 2, and 3 at a median follow-up of 21.1 months (range, 14.8-23.8), 9.2 months (range, 1.2-12.2), and 9.2 months (range, 3.7-11.5), respectively. See Table: MajesTEC-4/EMN30 Study (SRI Cohorts): Response Rates After ASCT and During Maintenance for additional details.
• In all the 3 SRI cohorts, 100% of evaluable patients achieved MRD negativity during maintenance. See Table: MajesTEC-4/EMN30 Study (SRI Cohorts): MRD Negativity (10⁵) in Evaluable Patients After ASCT and During Maintenance for additional details.
• The median progression free survival (PFS) was not reached in all cohorts.

Safety

• Treatment-emergent adverse events (TEAEs) of any grade were reported in 100% of patients in all Cohorts. Grade 3/4 TEAEs were reported in 100% of patients (n=32) in Cohort 1, 84.4% of patients (n=27) in Cohort 2, and in 56.7% of patients (n=17) in Cohort 3. Additional details are provided in Tables: MajesTEC-4/EMN30 Study (SRI Cohorts): Hematologic AEs and MajesTEC-4/EMN30 Study (SRI Cohorts): Nonhematologic AEs.
• Median relative dose intensity ranged from 95.5% to 99.7% for TECAVYLI and 58.4% to 61.5% for lenalidomide.
• Overall treatment discontinuation rate was 5.3% due to TEAEs.
• Cumulative incidence of grade 3/4 neutropenia at 6 months were 81.3% for Cohort 1, 56.3% for Cohort 2, and 40.0% for Cohort 3, respectively.
• No immune effector cell-associated neurotoxicity syndrome (ICANS) was reported.

Cytokine Release Syndrome

• Cytokine release syndrome (CRS) was reported in 50.0% of patients (n=16) in Cohort 1, 40.6% of patients (n=13) in Cohort 2, and in 43.3% of patients (n=12) in Cohort 3. All events were grade 1/2. The incidence of CRS was 37.2% after SUD 1, 8.5% after SUD 2 and 5.3% after treatment dose 1.
• No discontinuations were reported due to CRS.

Infections and Hypogammaglobulinemia

• Details on infections are provided in Table: MajesTEC-4/EMN30 Study (SRI Cohorts): Infections for details. One death due to coronavirus disease 2019 (COVID-19)-related TEAE was reported in SRI Cohort 2.
• Hypogammaglobulinemia (including patients with ≥1 TEAE of hypogammaglobulinemia or post-baseline immunoglobulin G [IgG] <400 mg/dL) was reported in 96.9% of patients (n=31) in Cohort 1, 78.1% of patients (n=25) in Cohort 2, and 93.3% of patients (n=28) in Cohort 3. All patients received ≥1 dose of intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIg).
• Prophylactic IVIG replacement was advised to maintain serum IgG levels of ≥400 mg/dL. Prophylaxis for Pneumocystis carinii/Pneumocystis jirovecii pneumonia and herpes zoster reactivation and routine antibiotic and antiviral prophylaxis were recommended.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 17 December 2024.